PB2213: EFFECTIVENESS OF CRIZANLIZUMAB IN REDUCING VASO-OCCLUSIVE CRISIS IN PATIENTS WITH SICKLE CELL DISEASE IN BRAZIL: STUDY PROTOCOL FOR AN OBSERVATIONAL, RETROSPECTIVE, MULTICENTER, NATIONAL STUDY
Authors: C. Bueno, L. Campos, A. Ritter, C. Zampirolli, R. Watanabe de Oliveira
Journal: HemaSphere (2022)

Background: Sickle cell disease (SCD) is a genetic condition resulting in a structurally abnormal hemoglobin, that leads to a cascade of physiologic consequences, including erythrocyte rigidity, vaso-occlusion, chronic anemia, hemolysis, and vasculopathy. Its management can be intensive, time-consuming, and costly. Few effective treatment options are currently available for these patients, specially to control the vaso-occlusive crisis (VOC). In March 2020, crizanlizumab, a monoclonal antibody drug, was approved by the Brazilian Health Regulatory Agency (ANVISA) to reduce the frequency of VOCs in patients with SCD. Crizanlizumab has been provided through Novartis Managed Access Program (MAP), classified in Brazil as Expanded Access Program (EAP), as an alternative therapy for SCD patients with an immediately life-threatening condition or serious disease. So far, limited evidence is available on crizanlizumab effectiveness and safety profile in Brazil and no real-world evidence study was conducted in the country. In this scenario, real-world studies present an essential role on complementing efficacy and safety data from pivotal and randomized studies in a much broader population profile. Aims: To describe the study design and rationale for investigation for the first real-world study assessing crizanlizumab in SCD patients in Brazil. The study aims to describe the effectiveness and safety profile of crizanlizumab treatment in patients with SCD in Brazil. Methods: This is an observational, retrospective, multi-center study based on secondary data of SCD patients treated with crizanlizumab in Brazil. In total, 98 patients treated with crizanlizumab within the Novartis MAP (EAP) will be screened for the study. Patients aged ≥ 16 ≤ 70 years old, diagnosed with SCD and with documented history of at least one VOC episode up to abstraction data initiation will be included in the study. Patient known to be participating in an interventional study at any point of the two-year study period and/or on a chronic transfusion program will be excluded. Data will be retrospectively abstracted from medical chart, considering one-year prior to crizanlizumab onset and up to one year of crizanlizumab treatment to assess the pattern of VOCs. The annual rate of VOC experienced by the patient and leading to a healthcare visit within the preceding 12-months prior to crizanlizumab initiation and 12-month after will be assessed and compared as the primary outcome. Secondary outcomes include the overall effectiveness of crizanlizumab over 1 year of treatment; time to next VOCs in SCD patients; safety aspects – including the frequency of adverse events of interest, e.g.: arthralgia, nausea, back pain, pyrexia, abdominal pain and infusion-related reactions in SCD patients during crizanlizumab treatment; clinical parameters in SCD management as well as demographics and clinical characteristics of SCD patients who were treated with crizanlizumab. Results: Study in progress. Results not yet available. Image:Summary/Conclusion: This is the first real world study to assess the effectiveness and safety of crizanlizumab in Brazilian SCD patients. It is expected that the assessment of SCD patients under MAP in Brazil will provide valuable information closer to what is expected in the real-world scenario. The availability of more robust evidence can support decision-making process, from clinical assessment by providers, to implementation of public healthcare policies.